the menopause and hrt. aims gain an understanding of what is meant by “menopause”, and how it is...
TRANSCRIPT
Aims
Gain an understanding of what is meant by “menopause”, and how it is diagnosed
Gain an understanding of the treatment options Think about the risks and benefits of HRT
Objectives
The menopause What is it? What are the symptoms? How should it be investigated?
HRT Indications Choice Risks Side effects
Alternatives to HRT
The menopause – what is it?
From the British Menopause Society: Permanent cessation of menstruation Only diagnosed after 12 months
spontaneous amenorrhoea – a retrospective diagnosis
Climacteric/perimenopause – period of change leading up to the menopause
The menopause – why does it happen?
Women are born with around 1.5m oocytes 1/3 are lost by the time of menarche. Most women menstruate about 400 times, and 20-
30 follicles start to develop each time. Eventually the supply of responsive oocytes in the
ovaries runs out
The menopause – hormonal changes
Ovarian follicular activity begins to fail as responsive oocytes run out
Leads to reduction in oestrogen and progesterone levels
Low level of oestrogen causes disruption of cycle and menopausal symptoms
-ve feedback loop causes rise in levels of luteinising hormone and follicle stimulating hormone
Epidemiology – UK
Final menstrual period usually occurs between the ages of 40 and 58, with an average age of 511
Final menstrual period below the age of 40 is considered to be premature menopause1
Evidence suggests that in the average woman symptoms start to increase from 2 years before the last menstrual period, reach a peak at 1 year following it, and have resolved by 8 years2
1) Nelson H; Lancet, 2008 Mar2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med. 2008 Sep
How common are symptoms?
80% of women experience menopausal symptoms1
45% of these find the symptoms distressing1
Most women manage the symptoms themselves – 10% seek medical advice for their symptoms2
1) RCPE, 2003
2) Roberts; BMJ, 2007
Symptoms
Menstrual irregularity Hot flushes/sweats Urinary/vaginal symptoms Sleep disturbance Mood changes Loss of libido Others
Menstrual irregularity
Cycle may lengthen to months, or shorten to weeks1
Increase in blood loss is common1
Majority of women experience irregularities, but 10% have a sudden cessation of menstruation2
1) Nelson H; Lancet, 2008 Mar
2) “Menopause”; Clinical Knowledge Summaries
Hot flushes/sweats
Common 70-80% of peri-menopausal women1
Tend to affect head, neck, face and chest. Usually last for a few minutes but can happen
multiple times during the day and night. Most common in the first year after the last menstrual
period2
1) RCPE 2003
2) “Menopause” Clinical Knowledge Summaries
Urinary/vaginal symptoms
Dyspareunia Vaginal discomfort/dryness Recurrent UTI Urinary incontinence Occur in 30% in early post-menopausal
period, rising to 47% later in life1
1) Grady; NEJM, 2006
Sleep disturbance and mood change
Sleep disturbance – commonly reported symptom, probably related to mood changes – anxiety, depression, memory loss, poor concentration1
Development of psychological symptoms has been linked to high BMI, and low amounts of physical activity2
1)Young T et al;. Sleep, 2003, Sep2) Di Donato P et al;. Maturitis, 2005, Nov
Loss of libido/other changes
Loss of libido may be related to hormonal changes, but also psychological factors, vaginal dryness, partner
Others (probably due to low oestrogen): Brittle nails Thinning of skin Hair loss Generalised aches and pains
Investigations
Generally not required, but blood tests include:
TFT FBC ?FSH LH, oestrogen and progesterone levels not
normally helpful
FSH1
Only needed if doubt about diagnosis – eg. in premature menopause
Can be very variable during peri-menopause – single measures are unreliable, and levels should be checked when women are not using any oestrogen containing medications (including COCP)
FSH > 30 is generally taken as post-menopausal range.
1) “Menopause” Clinical Knowledge Summaries
Associated problems1
Increased risk of cardiovascular disease + stroke
Increased risk of osteoporosis Redistribution of body fat ?Alzheimer’s Disease – more common in
women so may be hormonal link, but no evidence HRT reduces risk
1) British Menopause Society
HRT
Effective treatment for menopausal symptoms
Previously used widely and for prolonged periods
However: Women’s health initiative (2002) – increased risk of
coronary heart disease, stroke, breast cancer, PE Million women study (2003) – increased risk breast and
ovarian cancer
Indications for HRT1
Treatment of menopausal symptoms where the risk benefit ratio is favourable, in fully informed women, in the lowest possible dose needed to control symptoms and for the shortest possible time
In women with premature menopause until the age of natural menopause (50)
For prevention of osteoporosis in women unable to use other medications
1) “Menopause” Clinical Knowledge Summaries
Routes of delivery
Oral tablets Patches Creams/gels Nasal sprays IUS Oestrogen releasing vaginal ring S/C implants
Which preparation?
Questions:
1. Does the women have an intact uterus?
2. Are symptoms primarily vaso-motor or urogenital?
3. Systemic or local treatment?
4. Combined or oestrogen only?
5. Cyclical (oestrogen with progestogen from day 12-14) or continuous?
She has a uterus
Symptoms mainly vasomotor: Perimenopausal – Systemic cyclical combined HRT Postmenopausal – Systemic continuous combined HRT
Symptoms mainly urogenital: Perimenopausal – local oestrogen OR systemic cyclical
combined HRT Post menopausal – local oestrogen OR systemic continuous
combined HRT
She has no uterus
Symptoms mainly vasomotor – systemic oestrogen only HRT
Symptoms mainly urogenital – local oestrogen OR systemic oestrogen only HRT
Tibolone
Selective oestrogen receptor modulator Oestrogenic, progestogenic and androgenic properties Can be used if intact uterus and no bleeding for >1yr Evidence for improvement in sexual function and
vasomotor symptoms1
Increased risk of stroke and breast cancer, especially in over 60s2
Less risk with DVT and IHD
1) 1) Al-Azzawi et al; Obstet Gynecol 1999 Feb2) 2) Kenemans P et al; Lancet Oncol 2009 Feb
Contraindications to HRT1
Pregnancy and breast-feeding Undiagnosed vaginal bleeding VTE Active/recent angina or MI Suspected, current, or past breast Ca Endometrial Ca Active liver disease with abnormal LFTs
1) “Menopause”; Clinical Knowledge Summaries
What are the risks?
Venous thromboembolism Coronary heart disease Stroke Breast cancer Endometrial cancer Ovarian cancer
What are the risks?
Venous thrombo-embolism Increased risk of DVT and PE; highest risk in the
first year of use. Number of women having VTE/1000 over 5 years
(figures from BNF):
No HRT Oestrogen only HRT
Combined HRT
50-59 5 7 12
60-69 8 10 18
What are the risks?
Coronary heart disease Evidence for protection from CHD is lacking Increased risk of heart disease for women
starting combined HRT more than 10 years after the menopause (extra 15 cases/1000 women over 5 years)1
Rossouw JE et al; JAMA 2007, Apr
What are the risks?
Stroke Small increased risk of stroke for younger women on
HRT, rising in older women Number of women having stroke/1000 over 5 years
(figures from BNF):
No HRT Oestrogen only HRT
Combined HRT
50-59 4 5 5
60-69 9 12 12
What are the risks?
Breast cancer Increased risk is
proportional to the duration of treatment
Risk returns to untreated levels after 5 years
Number of women having breast cancer/1000 over 5 and 10 years (figures from BNF):
Over 5 years
No HRT Oestrogen only HRT
Combined HRT
50-59 10 12 16
60-69 15 18 24
Over 10 years
No HRT Oestrogen only HRT
Combined HRT
50-59 20 26 44
60-69 30 39 66
What are the risks?Endometrial cancer Substantial increased risk with oestrogen only HRT Use of progestogen eliminates risk, but needs to be weighed
against increased risk of breast cancer Number of women having endometrial cancer/1000 over 5 and
10 years (figures from BNF):No HRT – 5
yearsOestrogen
only HRT – 5 years
No HRT – 10 years
Oestrogen only HRT –
10 years
50-59 2 6 4 36
60-69 3 9 6 54
What are the risks?
Ovarian cancer Small increased risk of
ovarian cancer, rises with duration of use
Number of women having ovarian cancer/1000 over 5 and 10 years (figures from BNF)
Over 5 years
No HRT Oestrogen only HRT
Combined HRT
50-59 2 2 2
60-69 3 3 3
Over 10 years
No HRT Oestrogen only HRT
Combined HRT
50-59 4 5 5
60-69 6 8 8
Follow-up1
Initial follow up after 3 months Thereafter, a minimum of annual checks
Check effectiveness Side-effects BP + weight Breast examination – if appropriate Pelvic examination – if appropriate Review of risks/benefits
1) “Menopause”, Clinical Knowledge Summaries
Follow-up
Effectiveness – if symptom control not good consider: Poor absorption – eg. Bowel problem Drug interaction – eg. Carbemazepine, phenytoin Incorrect diagnosis – eg. Hypothyroidism, diabetes Patient expectations
Consider – increasing oestrogen dose, altering brand, changing delivery method
What are the side-effects?
Oestrogen: Breast tenderness Leg cramps Bloating Nausea Headaches
Bleeding – cyclical preparations produce regular and predictable bleeds, usually towards the end of the progestogen phase
Progestogen: Breast tenderness Backache Depression Pelvic pain
Oestrogen related side-effects
More likely to occur and be problematic when there has been a longer duration of ovarian failure
Often resolve with continued use Consider –
Breast tenderness – low fat, high carbohydrate diet Leg cramps – exercise and calf stretches Nausea, bloating – adjust timing of dose, take with food Headaches – try patches (may produce more stable
oestrogen levels)
Progestogen related side-effects
May be more problematic; may be connected to type, dose and duration of progestogen
Consider – Changing progestogen type Reducing dose Altering route to something other than oral “Long-cycle” HRT – (progestogen for 14 days every 3
months – only suitable if periods have stopped). Continuous combined therapy or tibolone (if post-
menopausal)
Managing bleeding
Heavy/prolonged bleeding – increase dose or duration of progestogen ?IUS
Bleeding early in progestogen phase – increase dose, change type of progestogen
Painful bleeding – change type of progestogen Irregular bleeding – increase progestogen No bleeding – may occur in 5% due to atropic
endometrium; confirm compliance and remember to exclude pregnancy!
Bleeding – when to refer?
Perimenopausal woman with intact uterus Change in pattern of withdrawal bleeds Breakthrough bleeding persisting for more than 6
months, or does not reduce on “long-cycle” HRT Persistent or unexplained bleeding after cessation of
hormone therapy for 6 weeks
Bleeding – when to refer?
Postmenopausal women with an intact uterus Breakthrough bleeding persists for more than 6 months
after starting HRT Bleeding occurs after amenorrhoea Persistent or unexplained bleeding after cessation of
hormone therapy for 6 weeks
But before changing treatment!
Pelvic examination – including visualising cervix
Confirm smears up to date TV USS
And don’t forget contraception!
HRT does not suppress ovulation – contraception is still needed
If an intact uterus: >50 – for one year after LMP <50 – for two years after LMP
Lifestyle measures1
Regular aerobic exercise Avoid triggers – caffeine, alcohol, smoking,
spicy food Wear light clothing Good sleep hygiene Weight loss
1) Alternatives to HRT for management of symptoms of menopause; ROCG (2006)
Medications1
SSRIs/SNRIs – fluoxetine, paroxetine, citalopram and venlafaxine have been shown to reduce symptoms; unlicensed for this use
Clonidine – evidence of efficacy in treating hot flushes, but high frequency of side-effects
Gabapentin – evidence of efficacy for treating hot flushes; for specialist use
1) Nelson HD et al; JAMA, 2006 May
Complementary therapies
Many OTC preparations available Black cohosh Evening primrose oil Dong quai Ginkgo biloba Ginseng St John’s Wort
Limited evidence of efficacy and long term safety Some preparations contain oestrogens Some preparations can interact with other
medications and may have other adverse side effects
Summary
The menopause is a natural and inevitable part of life
Menopausal symptoms are very common but most women never seek advice regarding management
Although HRT carries risks, it is a good and effective treatment for symptoms
Patients should be fully informed and allowed to make the decision themselves about whether to commence HRT